The use of antibodies, particularly monoclonal antibodies, has revolutionized several areas of basic and clinical research as well as routine diagnostic procedures. The clinical application of monoclonal antibodies has emerged as a major new source of drugs for cancer therapy. For example, antibodies to a surface protein called CD20 have dramatically improved the prognosis of NHL patients, as well as for those with antibody-mediated autoimmune diseases.
The development of high titers of neutralizing antibodies has been correlated with the ability of patients to fight off many viral infections. The recent spread of avian flu in South East Asia showed that those individuals who survived infections were also those people who were able to mount an effective B-cell antibody-dependent neutralizing response. Similar findings were shown a year earlier in the case of SARS survivors. It is estimated that the annual death toll in the United States that is caused by influenza amounts to 30,000 to 50,000 people annually. The global death toll from influenza is estimated to be 20 to 30 times higher that the figures for the US alone. The two populations who are especially vulnerable are young children and the elderly. The development of neutralizing antibodies that could be provided passively would dramatically decrease the mortality caused by influenza or other viruses, such as HIV.
As of May 2005, there were 18 therapeutic monoclonal antibody products on the US market. Worldwide, there were an estimated 500 monoclonal antibody products in development by more than 200 companies for the treatment of virtually every debilitating disease. Approximately 80 of these monoclonal antibody products are in clinical trials. The global market for monoclonal antibodies is projected to increase to $16.7 billion in 2008.
The traditional approaches to generate monoclonal antibodies rely on the hyperimmunization of mice, or other animals of choice. The antibody producing cells from the spleen are then collected and fused to a myeloma cell fusion partner. The selection for cells that retain their antibody production gene is accomplished by a forward and reverse selection procedure. While this has proven to be a very powerful technique, the limitations imposed by basic biology likely result in a loss of >90% of all the possible specificities that could be obtained. Some of those limitations involve a mechanism called “self-tolerance”, as well as certain requirements needed to attain a successful fusion between an antibody producing cell and a myeloma fusion partner.
Therefore, there is a need in the art for improved methods of generating antibodies that solve the problems related to the limitations listed above and lower the amount of time required to identify antibodies of interest.